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Engineered Platelet-Derived Growth Factor-Releasing Hydrogels Promote Fetal Membrane Healing In Vivo |
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| Authors: | Eva Avilla-Royo Ladina Vonzun Frauke Seehusen Queralt Vallmajo-Martin Flurina Famos Lukas Moser Katharina Gegenschatz-Schmid Lisa Amanda Krattiger Nele Strübing Miriam Weisskopf Ueli Moehrlen Nicole Ochsenbein-Kölble Martin Ehrbar |
| Affiliation: | 1. Department of Obstetrics, University Hospital Zurich, University of Zurich, Schmelzbergstrasse 12, 8091 Zurich, Switzerland;2. Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, University of Zurich, Winterthurerstrasse 268, 8057 Zurich, Switzerland;3. Center for Surgical Research, University Hospital Zurich, University of Zurich, Sternwartstrasse 14, 8091 Zurich, Switzerland;4. The Zurich Center for Fetal Diagnosis and Therapy, Frauenklinikstrasse 10, 8091 Zurich, Switzerland
Department of Pediatric Surgery, University Children's Hospital Zurich, University of Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland Children's Research Center, University Children's Hospital Zurich, University of Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland |
| Abstract: | Fetoscopic interventions to treat fetal anomalies are currently performed for a variety of conditions. Depending on the procedure, preterm rupture of the fetal membranes (FMs) happens in around 30% of the cases, potentially leading to preterm birth and fetal morbidity and mortality. Here, the capacity of modular transglutaminase crosslinked poly(ethylene glycol) (TG-PEG) hydrogels that release platelet-derived growth factor (PDGF)-BB to promote FM healing is described. In vitro, such growth factor-loaded hydrogels are able to stimulate amniotic cell migration and proliferation. When applied in vivo, these TG-PEG hydrogels tightly seal the FM and uterus defects created by a fetoscope and remain stable for 10 days. The migration of healing-related cells into such hydrogels in the myometrium, endometrium, and FM areas is only possible in soft TG-PEG hydrogels. Importantly, bioengineered hydrogels releasing PDGF-BB promote recruitment of host cells from the myometrium and the endometrium, and to a lesser extent from FM areas. In such hydrogels, the potent proliferation and matrix production of the recruited cells at the site of treatment into the biomaterial initiates a robust early healing response. PDGF-BB-loaded TG-PEG hydrogels hold great promise for the treatment of fetoscopy-induced FM defects and for the prevention of preterm birth. |
| Keywords: | amnion fetal membrane healing fetoscopy in vivo iPPROM |